Early events in HIV infection particularly the interplay between the virus and the initial host defense mechanisms, are likely to play major roles in determining the time frame or the subsequent progression to disease. understanding these components and how they dictate the outcome of this initial struggle between the virus and the host will provide important clues about the mechanism of HIV pathogenesis and correlates of protection against infection and disease progression. This program grant is dedicated to a comprehensive analysis of primary HIV infection ina unique study group from a highly endemic area of HIV transmission in Trinidad. The principal features of this cohort include large size, absence of bias for symptomatology, frequent sampling, long term follow-up for clinical endpoints and appropriately matched control subjects. The general aims of the study are to establish 1) relationships between early symptomatology and disease progression, 2) to provide a much finer resolution of the kinetic of HIV replication through frequent sampling and 3) to correlate a comprehensive range of host responses with viral replication. The ultimate goal of the program is to identify host responses that are most effective in suppressing HIV replication or in clearing the infection as well as those that are conducive to HIV dissemination and ultimately pathogenesis. Such information is likely to be important for design of preventive and therapeutic strategies that employ host defense mechanisms. The program is composed of four highly interactive projects led by experienced investigators that are tightly connected to a central Clinical Core. Overall management of the program will be effected by a Program Direction and Administration Core.